Microembolic Signals With Serial Transcranial Doppler Monitoring in Acute Focal Ischemic Deficit
A Local Phenomenon?
Background and Purpose The occurrence of microembolic signals (MES) in patients with transient ischemic attack (TIA) or stroke has already been described, but the diagnostic and prognostic value of this finding is still debated.
Methods We evaluated 90 consecutive patients admitted for their first hemispheric TIA or ischemic stroke within 72 hours of onset. All of them underwent 30-minute bilateral transcranial Doppler monitoring of middle cerebral arteries, within 72 hours of onset. The monitoring was repeated after an additional 24 hours and after 7 days. We then classified the episodes in the following etiologic categories: cardioembolic, atherothrombotic, small-vessel disease, mixed cases, unknown origin, and other causes.
Results We included 75 patients, with a mean interval of registration of 32.04±19.39 hours. There were 9 patients with MES (12%). All MES were recorded only on the symptomatic middle cerebral artery, and the majority were recorded during the first or the second registration. No statistically significant difference was found in risk factors and hematologic parameters. Five patients (56%) had atherothrombotic episodes, 3 patients (33%) had cardioembolic episodes, and 1 patient (11%) had a protein S deficit. No patient with MES had small-vessel disease (P=.01).
Conclusions MES are an infrequent finding in patients with TIA or ischemic stroke within 72 hours of onset, but they can be recorded more easily with serial registration. In our patients, MES were found only on the symptomatic middle cerebral artery and were present in atherothrombotic and cardioembolic episodes but not in small-vessel disease.
The occurrence of MES has already been described in patients with TIA or ischemic stroke.1 2 According to some authors, this finding might be related to the embolic origin of stroke and to recent previous episodes1 ; moreover, the presence of MES could have a negative prognostic value.1 2 3 All the previous studies evaluated MES in a single registration1 2 3 4 and with a different time interval from stroke onset, from 48 hours1 4 to 4 weeks.2 The aim of the present study was to evaluate the prevalence of MES in patients with acute focal ischemic deficit, by use of serial transcranial Doppler recording, and to correlate them with the etiology of the ischemic episode.
Subjects and Methods
We evaluated 90 patients consecutively admitted to our Stroke Unit for their first focal ischemic neurological deficit involving the vascular territory of MCAs. We considered both TIAs and complete strokes and excluded patients with cerebral hemorrhage and with vertebrobasilar episodes. All of the patients underwent a 30-minute bilateral transcranial Doppler monitoring of their MCAs (Multidop DWL X, Sipplingen) for the identification of MES. A single long-term experienced examiner (S.A.), who was present for the duration of the monitoring, performed the recording. We used the following criteria for the diagnosis of MES: unidirectionality, duration of <300 milliseconds, and intensity of >8 dB above the Doppler background.5 The gain background was adjusted in every case to the appropriate value by the operator. The trigger level for the embolus detection algorithm was determined automatically: if the program finds an amplitude above these values, it searches the spectral lines between the suspicious FFT line and the zero line for confirmation that this is not an artifact. We then differentiated MES from artifacts by personally analyzing on-line every single phenomenon. In case of uncertainty, the recorded monitoring was discussed with the other authors (M.D.S. and C.F.), and a consensus was reached. The monitoring was performed within 72 hours of stroke onset, after an additional 24 hours, and after 7 days. All the patients were evaluated with the complete diagnostic protocol of our unit, which included clinical history, neurological examination, at least two CT scans, carotid duplex, routine transcranial Doppler, ECG-Holter monitoring, transthoracic echocardiography, and, only in selected cases, cerebral MRI, transesophageal echocardiography, and cerebral angiography. Patients were treated with antiplatelet agents (acetylsalicylic acid) or anticoagulants (heparin or warfarin) or, in particular cases (2 patients), both agents; 1 patient had not received any antithrombotic treatment in the acute phase. The ischemic episode was then classified in the following etiologic categories: atherothrombotic, cardioembolic, small-vessel disease, mixed cases, unknown origin, and other causes.6 Prognosis was evaluated at 30 days from onset, giving each patient a score according to the Oxford Disability Scale and giving a score of 6 for deceased patients.7 The etiologic and prognostic classification was done by one of the authors (C.G.), who was blind to the transcranial Doppler results.
We included 75 patients, 51 men and 24 women, with a mean age of 69.43±13.85 (mean±SD; range, 25 to 80) years. Fifteen patients were excluded because of insufficient temporal window or diagnostic mistake. The mean interval of registration was 32.04±19.39 (range, 1 to 72) hours. Nine patients (12%) of 75 showed MES in at least one of the three registrations. MES were recorded only on the symptomatic MCA, irrespective of the diagnostic group. Most of the MES-positive patients (8 [88%] of 9) showed MES in the second registration, whereas 4 (44%) of 9 were positive in the first recording, and only 1 (11%) had MES in the third registration; 5 patients who did not show MES in the first registration (56% of the whole group) became positive after 24 hours (Table 1⇓). The analysis of the difference between the group with MES and the group without MES showed no statistically significant differences in the distance of recording from onset, stroke risk factors (age, hypertension, atrial fibrillation, diabetes, dyslipidemia, smoking, and presence of ipsilateral carotid stenosis), and hematological parameters (platelet count, hematocrit, fibrinogen, and prothrombin time). There was no difference in type of episode (TIA or stroke), previous episodes, or presence of silent brain infarctions on CT scan; moreover, there was no difference in prognosis and in therapeutic regimen (Table 2⇓).
Five patients with MES (56%) were classified in the atherothrombotic group, 3 patients (33%) were cardioembolic, and 1 patient (11%) had a protein S deficit. No patient with MES was classified as having small-vessel disease. All of the 5 patients classified as having had atherothrombotic episodes had ipsilateral carotid stenosis of >60% or carotid occlusion; the other 4 patients classified in other diagnostic categories had normal carotid duplex or slight atherosclerotic changes without stenosis.
The comparison between patients with small-vessel disease and patients with cardioembolic or atherothrombotic episodes showed a significant difference (P=.01) (Table 3⇓).
The occurrence of MES is not a frequent finding in our series, being present overall in 12% of the patients. We showed that serial registration is useful in recording the presence of MES: they were recorded in 44% of MES-positive patients within 72 hours, in 88% after an additional 24 hours, and in 11% after 1 week. Other authors have reported a prevalence of MES in the acute phase. Grosset et al4 evaluated 41 patients within 48 hours and found MES in 71% of the patients.4 Tong and Albers1 reported MES in 11% of 38 patients within 48 hours from onset. More recent studies have reported a prevalence of 29% in selected patients with carotid stenosis evaluated within 12 days3 and 9.3% in 280 unselected acute patients evaluated within 4 weeks.2 All of these authors performed a single 30-minute registration. The monitoring period of 30 minutes might be too short to detect MES,8 but it has been chosen as a compromise, considering also the frequently poor compliance of acute stroke patients. The different prevalence reported in the literature can be due to different criteria for the identification of MES and to different timing of registrations. Forteza et al,3 analyzing a selected sample of patients with symptomatic carotid stenosis, reported a higher occurrence of MES in patients examined within 4 days compared with patients recorded within 12 days.3 Takada et al,9 studying 29 patients with acute ischemic stroke, reported a lower frequency of MES with longer distance from event (from 1 day to 28 days). In our series, the prevalence of MES is low in the third registration (1 week after the first recording), but 56% of the whole group with MES were negative at 72 hours but showed MES after an additional 24 hours. Sliwka et al,10 monitoring patients with stroke within 1 week from onset, performed multiple registration (at admission, after 24 hours, and after 48 hours) and found MES in 51% of the patients. We suggest that a serial examination can allow us to increase the sensitivity of monitoring in acute stroke patients and might be a partial solution to the problem of the time of monitoring, waiting for simple long-term monitoring equipment.
Some authors have already reported a higher prevalence of MES in atherothrombotic or cardioembolic stroke compared with lacunar syndromes or lacunar infarctions.2 4 Grosset et al,4 studying 45 patients within 48 hours of onset, did not find MES in 8 patients with small-vessel disease. Daffertshofer et al2 reported 4.5% of MES in patients with small-vessel disease, as opposed to 14.2% in large-vessel disease; moreover, none of the patients with lacunar infarction on CT scan showed MES. Our findings are in agreement with these data and suggest that a cardiac or artery-to-artery embolic event might be necessary to develop local particles to be recorded, whereas in small-vessel disease a different process may lead to the small-artery occlusion, without any signal in the main MCA trunk.
In all of our patients, MES were recorded only on the symptomatic side, irrespective of the etiologic categories of the single patient. Some authors reported that MES in acute stroke can be recorded ipsilaterally to carotid stenosis or bilaterally, in patients with cardioembolic stroke.4 In our 3 patients with cardioembolic stroke, MES were recorded only on the symptomatic MCA. Sliwka et al10 reported a unilateral occurrence of MES in 8 (62%) of 13 patients with cardioembolic stroke. Other authors reported a hemispheric side preference of cardiac valvular emboli in individual patients, suggesting a possible explanation of the clinical observation of lodging preferences of recurrent cardiac embolism.11 12 An alternative explanation of the unilateral presence of MES in the acute phase of TIA or stroke could be a local spontaneous clotting and thrombolysis phenomenon,13 14 but it needs to be confirmed by larger samples.
In our patients, MES are not related to a previous clinical event or silent brain infarctions, in disagreement with Tong and Albers,1 who have reported MES to be correlated with a previous recent event. Our different findings might be due to the larger number of patients and to the serial registration we used. MES were not related to 30-day prognosis nor to therapeutic regimen (Table 2⇑), in agreement with other findings, even if the therapeutic implication of MES is not yet clarified.2 15
In conclusion, our data confirm that MES are an infrequent finding in patients with acute TIA or stroke within 72 hours and that serial registrations may increase the sensitivity of the recording. MES recorded in the acute phase of ischemic episodes may have a pathophysiological meaning, being correlated to the embolic origin of the event and, possibly, to local clotting phenomena.
Selected Abbreviations and Acronyms
|FFT||=||fast Fourier transform|
|MCA||=||middle cerebral artery|
|TIA||=||transient ischemic attack|
This study was partially supported by the University of Genova, Italy.
Presented in part at the Joint 3rd World Congress and 5th European Stroke Conference, Munich, Germany, September 1-4, 1996.
- Received February 10, 1997.
- Revision received April 18, 1997.
- Accepted April 28, 1997.
- Copyright © 1997 by American Heart Association
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